We have been studying the mechanisms of mitogen and antigen hyporesponsiveness during CMV mononucleosis. This hyporesponsiveness is reversible by in vitro culture or by removal of adherent mononuclear cells. Addition of fresh adherent mononuclear cells can further diminish the responsiveness. T lymphoblastoid (CEM) cell lines persistently infected with herpes simplex virus (HSV) have been maintained. Depending on manipulations of these cells, they can become productively or latently infected. Treatment of productively infected cells with Concanavalin-A (Con-A) can markedly reduce or eliminate productive infection, although HSV-genetic material persists in such cells. In contrast, treatment of latently infected cells with Phytohemagglutinin (PHA) can activate virus and induce productive HSV infection. CEM T lymphoblasts have also been persistently and productively infected with the simian sarcoma virus (SSV). Infection did not affect spontaneous or PHA-induced blastogenesis, as measured by incorporation of tritiated thymidine. In constrast, preliminary studies suggest that infection with SSV may confer autoreactive potential upon these cells, when studied in a microcytoxicity assay against histocompatible fibroblasts.